Untargeted metabolomic profiling reveals molecular signatures associated with type 2 diabetes in Nigerians
Abstract Background Type 2 diabetes (T2D) has reached epidemic proportions globally, including in Africa. However, molecular studies to understand the pathophysiology of T2D remain scarce outside Europe and North America. The aims of this study are to use an untargeted metabolomics approach to ident...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-03-01
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| Series: | Genome Medicine |
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| Online Access: | https://doi.org/10.1186/s13073-024-01308-5 |
| _version_ | 1797273661600694272 |
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| author | Ayo P. Doumatey Daniel Shriner Jie Zhou Lin Lei Guanjie Chen Omolara Oluwasola-Taiwo Susan Nkem Adela Ogundeji Sally N. Adebamowo Amy R. Bentley Mateus H. Gouveia Karlijn A. C. Meeks Clement A. Adebamowo Adebowale A. Adeyemo Charles N. Rotimi |
| author_facet | Ayo P. Doumatey Daniel Shriner Jie Zhou Lin Lei Guanjie Chen Omolara Oluwasola-Taiwo Susan Nkem Adela Ogundeji Sally N. Adebamowo Amy R. Bentley Mateus H. Gouveia Karlijn A. C. Meeks Clement A. Adebamowo Adebowale A. Adeyemo Charles N. Rotimi |
| author_sort | Ayo P. Doumatey |
| collection | DOAJ |
| description | Abstract Background Type 2 diabetes (T2D) has reached epidemic proportions globally, including in Africa. However, molecular studies to understand the pathophysiology of T2D remain scarce outside Europe and North America. The aims of this study are to use an untargeted metabolomics approach to identify: (a) metabolites that are differentially expressed between individuals with and without T2D and (b) a metabolic signature associated with T2D in a population of Sub-Saharan Africa (SSA). Methods A total of 580 adult Nigerians from the Africa America Diabetes Mellitus (AADM) study were studied. The discovery study included 310 individuals (210 without T2D, 100 with T2D). Metabolites in plasma were assessed by reverse phase, ultra-performance liquid chromatography and mass spectrometry (RP)/UPLC-MS/MS methods on the Metabolon Platform. Welch’s two-sample t-test was used to identify differentially expressed metabolites (DEMs), followed by the construction of a biomarker panel using a random forest (RF) algorithm. The biomarker panel was evaluated in a replication sample of 270 individuals (110 without T2D and 160 with T2D) from the same study. Results Untargeted metabolomic analyses revealed 280 DEMs between individuals with and without T2D. The DEMs predominantly belonged to the lipid (51%, 142/280), amino acid (21%, 59/280), xenobiotics (13%, 35/280), carbohydrate (4%, 10/280) and nucleotide (4%, 10/280) super pathways. At the sub-pathway level, glycolysis, free fatty acid, bile metabolism, and branched chain amino acid catabolism were altered in T2D individuals. A 10-metabolite biomarker panel including glucose, gluconate, mannose, mannonate, 1,5-anhydroglucitol, fructose, fructosyl-lysine, 1-carboxylethylleucine, metformin, and methyl-glucopyranoside predicted T2D with an area under the curve (AUC) of 0.924 (95% CI: 0.845–0.966) and a predicted accuracy of 89.3%. The panel was validated with a similar AUC (0.935, 95% CI 0.906–0.958) in the replication cohort. The 10 metabolites in the biomarker panel correlated significantly with several T2D-related glycemic indices, including Hba1C, insulin resistance (HOMA-IR), and diabetes duration. Conclusions We demonstrate that metabolomic dysregulation associated with T2D in Nigerians affects multiple processes, including glycolysis, free fatty acid and bile metabolism, and branched chain amino acid catabolism. Our study replicated previous findings in other populations and identified a metabolic signature that could be used as a biomarker panel of T2D risk and glycemic control thus enhancing our knowledge of molecular pathophysiologic changes in T2D. The metabolomics dataset generated in this study represents an invaluable addition to publicly available multi-omics data on understudied African ancestry populations. |
| first_indexed | 2024-03-07T14:47:31Z |
| format | Article |
| id | doaj.art-4d020d773e6245dab0caa4b6f73e88be |
| institution | Directory Open Access Journal |
| issn | 1756-994X |
| language | English |
| last_indexed | 2024-03-07T14:47:31Z |
| publishDate | 2024-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Genome Medicine |
| spelling | doaj.art-4d020d773e6245dab0caa4b6f73e88be2024-03-05T19:51:43ZengBMCGenome Medicine1756-994X2024-03-0116111810.1186/s13073-024-01308-5Untargeted metabolomic profiling reveals molecular signatures associated with type 2 diabetes in NigeriansAyo P. Doumatey0Daniel Shriner1Jie Zhou2Lin Lei3Guanjie Chen4Omolara Oluwasola-Taiwo5Susan Nkem6Adela Ogundeji7Sally N. Adebamowo8Amy R. Bentley9Mateus H. Gouveia10Karlijn A. C. Meeks11Clement A. Adebamowo12Adebowale A. Adeyemo13Charles N. Rotimi14Center for Research On Genomics and Global Health, National Human Genome Research Institute, National Institutes of HealthCenter for Research On Genomics and Global Health, National Human Genome Research Institute, National Institutes of HealthCenter for Research On Genomics and Global Health, National Human Genome Research Institute, National Institutes of HealthCenter for Research On Genomics and Global Health, National Human Genome Research Institute, National Institutes of HealthCenter for Research On Genomics and Global Health, National Human Genome Research Institute, National Institutes of HealthDepartment of Medicine, Ring Road State HospitalCenter for Bioethics & ResearchCenter for Bioethics & ResearchDepartment of Epidemiology and Public Health, and the Greenebaum Comprehensive Cancer Center, University of Maryland School of MedicineCenter for Research On Genomics and Global Health, National Human Genome Research Institute, National Institutes of HealthCenter for Research On Genomics and Global Health, National Human Genome Research Institute, National Institutes of HealthCenter for Research On Genomics and Global Health, National Human Genome Research Institute, National Institutes of HealthDepartment of Epidemiology and Public Health, and the Greenebaum Comprehensive Cancer Center, University of Maryland School of MedicineCenter for Research On Genomics and Global Health, National Human Genome Research Institute, National Institutes of HealthCenter for Research On Genomics and Global Health, National Human Genome Research Institute, National Institutes of HealthAbstract Background Type 2 diabetes (T2D) has reached epidemic proportions globally, including in Africa. However, molecular studies to understand the pathophysiology of T2D remain scarce outside Europe and North America. The aims of this study are to use an untargeted metabolomics approach to identify: (a) metabolites that are differentially expressed between individuals with and without T2D and (b) a metabolic signature associated with T2D in a population of Sub-Saharan Africa (SSA). Methods A total of 580 adult Nigerians from the Africa America Diabetes Mellitus (AADM) study were studied. The discovery study included 310 individuals (210 without T2D, 100 with T2D). Metabolites in plasma were assessed by reverse phase, ultra-performance liquid chromatography and mass spectrometry (RP)/UPLC-MS/MS methods on the Metabolon Platform. Welch’s two-sample t-test was used to identify differentially expressed metabolites (DEMs), followed by the construction of a biomarker panel using a random forest (RF) algorithm. The biomarker panel was evaluated in a replication sample of 270 individuals (110 without T2D and 160 with T2D) from the same study. Results Untargeted metabolomic analyses revealed 280 DEMs between individuals with and without T2D. The DEMs predominantly belonged to the lipid (51%, 142/280), amino acid (21%, 59/280), xenobiotics (13%, 35/280), carbohydrate (4%, 10/280) and nucleotide (4%, 10/280) super pathways. At the sub-pathway level, glycolysis, free fatty acid, bile metabolism, and branched chain amino acid catabolism were altered in T2D individuals. A 10-metabolite biomarker panel including glucose, gluconate, mannose, mannonate, 1,5-anhydroglucitol, fructose, fructosyl-lysine, 1-carboxylethylleucine, metformin, and methyl-glucopyranoside predicted T2D with an area under the curve (AUC) of 0.924 (95% CI: 0.845–0.966) and a predicted accuracy of 89.3%. The panel was validated with a similar AUC (0.935, 95% CI 0.906–0.958) in the replication cohort. The 10 metabolites in the biomarker panel correlated significantly with several T2D-related glycemic indices, including Hba1C, insulin resistance (HOMA-IR), and diabetes duration. Conclusions We demonstrate that metabolomic dysregulation associated with T2D in Nigerians affects multiple processes, including glycolysis, free fatty acid and bile metabolism, and branched chain amino acid catabolism. Our study replicated previous findings in other populations and identified a metabolic signature that could be used as a biomarker panel of T2D risk and glycemic control thus enhancing our knowledge of molecular pathophysiologic changes in T2D. The metabolomics dataset generated in this study represents an invaluable addition to publicly available multi-omics data on understudied African ancestry populations.https://doi.org/10.1186/s13073-024-01308-5MetabolomicsType 2 diabetesAfricansBiomarkers |
| spellingShingle | Ayo P. Doumatey Daniel Shriner Jie Zhou Lin Lei Guanjie Chen Omolara Oluwasola-Taiwo Susan Nkem Adela Ogundeji Sally N. Adebamowo Amy R. Bentley Mateus H. Gouveia Karlijn A. C. Meeks Clement A. Adebamowo Adebowale A. Adeyemo Charles N. Rotimi Untargeted metabolomic profiling reveals molecular signatures associated with type 2 diabetes in Nigerians Genome Medicine Metabolomics Type 2 diabetes Africans Biomarkers |
| title | Untargeted metabolomic profiling reveals molecular signatures associated with type 2 diabetes in Nigerians |
| title_full | Untargeted metabolomic profiling reveals molecular signatures associated with type 2 diabetes in Nigerians |
| title_fullStr | Untargeted metabolomic profiling reveals molecular signatures associated with type 2 diabetes in Nigerians |
| title_full_unstemmed | Untargeted metabolomic profiling reveals molecular signatures associated with type 2 diabetes in Nigerians |
| title_short | Untargeted metabolomic profiling reveals molecular signatures associated with type 2 diabetes in Nigerians |
| title_sort | untargeted metabolomic profiling reveals molecular signatures associated with type 2 diabetes in nigerians |
| topic | Metabolomics Type 2 diabetes Africans Biomarkers |
| url | https://doi.org/10.1186/s13073-024-01308-5 |
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